Alzheimer’s disease is a progressive neurodegenerative disorder and the leading cause of dementia in the elderly. Characterized by cognitive decline and memory impairment, the disease is closely linked to the accumulation of misfolded proteins, particularly amyloid-β and tau. Tau, a microtubule-associated protein, undergoes pathological phosphorylation, leading to the formation of insoluble neurofibrillary tangles. These tau aggregates propagate in a prion-like manner across brain networks, contributing to disease progression. This review explores the molecular mechanisms underlying tau misfolding, aggregation, and trans-synaptic spread. By examining the structural dynamics of tau and amyloid-β oligomers, the review highlights current insights into tauopathies and emphasizes the need for targeted therapeutic strategies against tau-related neurodegeneration. Alzheimer’s disease is the most prevalent neurodegenerative disorder which leads to dementia. The disease establishes in the later stages of life and can lead to cognitive decline, characterised by memory loss, disorientation, impaired cognition and alterations in personality and mood. The risk of developing Alzheimer’s dementia intensifies sharply with advancing age. Misfolded protein aggregation initiates Alzheimer’s disease pathology. Protein misfolding can arise from a complex interplay of factors, including genetic mutations, translational inaccuracies and dysfunctional protein modifications. The misfolding of one protein leads to the misfolding of other proteins, resulting in the formation of further aggregates. Histopathological analysis of Alzheimer’s disease tissue reveals the presence of tau protein deposits. Tau is a microtubule-associated protein essential for axonal stability, and disruptions in its phosphorylation/dephosphorylation balance lead to microtubule dissociation and aggregation. Phosphorylated tau undergoes a hierarchical assembly, progressing from oligomers to fibrils and culminating in neurofibrillary tangles. The accumulation of neurofibrillary tangles spreads in specific spatiotemporal patterns in a prion-like manner that aligns with brain network connections, with aggregated tau serving as a seed for recruiting and aggregating soluble tau. Additionally, tau aggregates can be released into the extracellular space and taken up by other neurons, further promoting the spread of the pathology. This interneuronal transmission may be a key factor in the progression of tauopathies in the brain and also suggesting that tauopathy is transmitted through trans-synaptic pathways. Moreover, by probing the molecular architecture and aggregation dynamics of amyloid-β and tau oligomers, this review illuminates the underlying mechanisms driving Alzheimer’s disease pathology. Further research is essential to understand the mechanisms of tau pathology and to develop effective treatments for tauopathies. Investigating the structural and functional properties of tau protein, along with the molecular mechanisms behind tau pathology, is vital for creating new therapies for these challenging diseases.